Magnetic Cell Labeling of Primary and Stem Cell-Derived Pig Hepatocytes for MRI-Based Cell Tracking of Hepatocyte Transplantation

Roach, Dwayne R.; Garrett, Wesley M.; Welch, G. Rickey; Caperna, Thomas J.; Talbot, Neil C.; Shapiro, Erik M.

doi:10.1371/journal.pone.0123282

Cited by 5 publications

(3 citation statements)

References 59 publications

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“…Cellular magnetic resonance imaging (MRI) is an important methodology that can visualize and track cells labeled with MRI contrast agents in vivo 1 2 3 4 5 6 7 8 9 10 11 12 13 . Cellular MRI is essential to regenerative medicine, allowing monitoring the delivery of stem cells and/or immune cells to the desired sites in the body.…”

mentioning

confidence: 99%

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

Liu

Tseng

et al. 2016

Sci Rep

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Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new “bio-mimicry” method by making use of the “in-vivo environment” of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies.

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mentioning

confidence: 99%

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

Liu

Tseng

et al. 2016

Sci Rep

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“…Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label macrophages for MRI-based cell tracking in vivo [ 172 ]. Similarly, magnetic labeling of primary and stem cell-derived pig hepatocytes has been employed for MRI-based cell tracking [ 173 ]. In addition, PLGA encapsulated magnetic nano- and micro-particles and photoconvertible near-infrared lipophilic cell membrane dyes have also been employed [ 174 , 175 ].…”

Section: Routes Of Cell Delivery and Associated Challengesmentioning

confidence: 99%

Liver cell therapy: is this the end of the beginning?

Alwahsh

Rashidi

Hay

2017

Cell. Mol. Life Sci.

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The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration.

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“…Importantly, newer technologies, including the use of cells labeled with micron-sized iron oxide particles (MPIO), have shown the capacity to detect single cells by MRI (102–105). Recently, investigators were able to show that porcine hepatocytes could successfully be labeled with MPIO and still maintain their multitude of metabolic functions (106). However, a recurrent challenge is the ability to quantify the number of cells being detected and to confirm that the signal detected is actually an engrafted hepatocyte and not uptake by kuppfer cells or macrophages after hepatocytes have been destroyed.…”

Section: Improving Transplanted Hepatocyte Survival and Monitoringmentioning

confidence: 99%

Clinical Hepatocyte Transplantation: What Is Next?

et al. 2017

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Purpose of review Significant recent scientific developments have occurred in the field of liver repopulation and regeneration. While techniques to facilitate liver repopulation with donor hepatocytes and different cell sources have been studied extensively in the laboratory, in recent years clinical hepatocyte transplantation (HT) and liver repopulation trials have demonstrated new disease indications and also immunological challenges that will require the incorporation of a fresh look and new experimental approaches. Recent findings Growth advantage and regenerative stimulus are necessary to allow donor hepatocytes to proliferate. Current research efforts focus on mechanisms of donor hepatocyte expansion in response to liver injury/preconditioning. Moreover, latest clinical evidence shows that important obstacles to HT include optimizing engraftment and limited duration of effectiveness, with hepatocytes being lost to immunological rejection. We will discuss alternatives for cellular rejection monitoring, as well as new modalities to follow cellular graft function and near-to-clinical cell sources. Summary HT partially corrects genetic disorders for a limited period of time and has been associated with reversal of ALF. The main identified obstacles that remain to make HT a curative approach include improving engraftment rates, and methods for monitoring cellular graft function and rejection. This review aims to discuss current state-of-the-art in clinical HT and provide insights into innovative approaches taken to overcome these obstacles.

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Magnetic Cell Labeling of Primary and Stem Cell-Derived Pig Hepatocytes for MRI-Based Cell Tracking of Hepatocyte Transplantation

Cited by 5 publications

References 59 publications

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

Liver cell therapy: is this the end of the beginning?

Clinical Hepatocyte Transplantation: What Is Next?

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